USP and Ph. Eur. Initiatives in the Biologics Arena Continue to Bear Fruit; FDA Joins the Pharmacopeias in Upgrading Particulate Guidance


The emerging biotech product modalities and their complex analytical challenges and needs have led USP and the European Pharmacopoeia to adapt their standard-setting approaches and work collaboratively with stakeholders internationally in setting and pursuing priorities.

● Part I: Update on USP’s Evolving Role and Current Initiatives In the Biologics Arena

This part of the story focuses on a review of USP’s evolving role and current standard-setting initiatives in the biologics arena provided by its Global Biologics VP Fouad Atouf at a PDA conference in October 2021. General chapters on analytical QbD and the testing of mAbs and mRNA vaccines, standards to support characterization of advanced therapies, and best practices for precision medicines and genomics are among the current focal points of USP’s efforts to support the rapidly evolving biotech product development, manufacturing, and control needs.

● Part II: European Pharmacopoeia and FDA Join USP in Focusing on Particulate Control

Part II narrows the focus onto the analysis and control of particulates. Building on a December 2021 EDQM webinar conducted by European Pharmacopoeia experts, the second part explores how Ph. Eur., the tripartite Pharmacopoeial Discussion Group (PDG), and FDA are joining with USP in upgrading the standards and guidance needed to address the particulate concerns that biotech products present as their complexity and formulation challenges increase and the analytical toolset gets more powerful. Ph. Eur. and USP monographs and chapters are being revised and harmonized to advance particulate control, and the FDA has issued draft guidance on inspecting injectables for visible particulates.

USP Leadership Has Been Active in Biologic Standards Dialogue

Atouf’s remarks at the October conference represented an update on another similar presentation he gave two years earlier at the fall 2019 PDA/FDA conference (see IPQ October 27, 2019). At that 2019 meeting he shed additional light on how USP’s standard-setting approach has been evolving and becoming more collaborative to better support the manufacturing, evaluation, and control needs of the new generation of biologics and other complex products.

The compendia has evolved, he explained, from “a book of pharmacopeial recipes, where the recipes describe how you make a pharmaceutical preparation,” to providing “descriptions of sophisticated procedures that are used to address quality attributes of specific products.”

At the fall 2019 conference, he discussed USP’s engagement with six prominent biologicals – insulin, somatropin, filgrastim, interferon, monoclonal antibodies, and CD34 stem cells – to show how compendial standards-setting has been moving toward a performance-based approach as the products get more complex. “Instead of looking at a standard that allows the user to demonstrate that they meet market specifications,” USP needed to “start looking at standards that allow the user to demonstrate method and process performance,” Atouf explained.

The strategy to evolve from a monograph approach to more broadly applicable standards that would reach across the product/process/analytics lifecycle for biologics had been recognized in a resolution passed at USP’s 2015 convention. It called for a paradigm shift that would best facilitate innovation and availability and serve the pharmacopeia’s public health mission.

USP leadership has also had a chance to discuss the pharmacopeia’s evolving role and current initiatives in the biologic standards arena – and the impact of and learnings from the pandemic – at other recent venues.

At the June 2020 PDA Europe annual meeting, USP Global Biologics Senior Scientific Fellow Maura Kibbey highlighted the cooperation needed between industry, regulators, and pharmacopeias around the world and sharing of the standards to assure consistent expectations, and she explained how USP’s more active involvement in ICH is one facet of the effort to expand this cooperation (see IPQ Nov. 9, 2020).

At the fall 2020 PDA pharmacopeia conference, CEO Ron Piervincenzi reviewed how improved understanding of supply chain vulnerabilities and providing support for vaccine development have been two facets of the USP effort to help address the pressing challenges that the pandemic has brought to the fore (see IPQ November 9, 2020 for the full presentations by Kibbey and Piervincenzi).

USP has been engaging in an in-depth medicines supply mapping project with the goal of improving the understanding of the complex linkages and create transparency about how medicines flow around the world so that the vulnerabilities can be better characterized, predicted and mitigated.

To help improve vaccine access while safeguarding quality, Piervincenzi explained, USP has also been focusing on enhancing its physical and documentary standards that support vaccine manufacturing development, scale-up, and delivery, and providing related technical assistance and educational opportunities in a variety of forms.

Also addressing the PDA pharmacopeia conference, Science & Standards Liaison Sarita Acharya shed additional light on USP’s multifaceted efforts to support COVID vaccine/treatment development and distribution and how these efforts fit in with its ongoing strategic plan for strengthening engagement in the biologics arena.

A panel discussion followed on the conference’s third day, further exploring the pandemic’s impact on pharmacopeia, industry, and regulatory agency operations and how they communicate and collaborate. [See IPQ December 23, 2020 for a review of the panel discussions.]

EDQM Leadership Weighs in on Ph. Eur. Biologics Standard Setting Efforts

The pandemic has also bolstered the EDQM/Ph. Eur. efforts to adapt its standard-setting approaches and enhance its contribution to vaccine and therapy quality, analytical technologies, and supply management.

Joining Kibbey at the PDA Europe annual meeting was Ph. Eur. Department Head Cathie Vielle. She provided a similar review of Ph. Eur. developments in standard setting for biologics and how the pharmacopoeia’s efforts support industry and complement those of regulatory agencies and their collaboration through ICH and WHO.

Further insight on the role that EDQM and Ph. Eur. play in medicine quality was provided by EDQM CEO Susanne Keitel in her keynote presentation at the June 2019 conference held in Strasbourg, France in conjunction with the release of the 10th edition of Ph. Eur, where she explored EDQM’s evolution, what it has achieved, and its goals. [See also IPQ December 23, 2020 for more on the Vielle and Keitel presentations and EDQM’s pandemic response.]

The collaboration and harmonization that takes place through the PDG continues to be seen as an important contributor to the pharmacopoeial efforts to keep pace with the advancing technology.

EDQM announced in October that the PDG – which brings together the Ph. Eur., USP and Japanese Pharmacopoeia (JP) and includes WHO as an observer – is preparing a pilot scheme to integrate additional pharmacopoeias. The release emphasized that “this is a critical step in the PDG’s commitment to expanding recognition of harmonised pharmacopoeial standards with a view to achieving global convergence.” [A link to the release is provided below.]

Also in October 2021, after 15 years at SwissMedic and a year at WHO, Petra Dörr took over the EDQM helm from Susanne Keitel.

Before becoming EDQM director in 2007, Keitel had been a quality management leader at the German drug/device regulatory agency BfArm, where she was active in ICH and other international and pharmacopeial activities.

At Swissmedic, Dörr played a leading role in the agency’s international collaboration and communications activities, including serving on the management committees of ICH and the International Pharmaceutical Regulators Forum (IPRF) – and ultimately chairing IPRF and vice-chairing the ICH Assembly. At WHO, she engaged in its regulatory system strengthening and convergence efforts.


●  EDQM release on PDG expansion


Here is a listing of IPQ’s coverage of the dialogue that has been taking place on: ● the evolving standards and guidance needs in the biotech arena, and the pharmacopeial role and initiatives in helping fill them, and ● the impact from the pandemic on these efforts and relevant learnings. Included are the links to the stories, which include all of those cited in this introduction.

Biomanufacturer Raw Material Control on Regulatory Front Burner as Analytical Power and Formulation Challenges Intensify — September 9, 2021

Part I: Biotech Regulator Vantage Point on Raw Material Control
Part II: The Added Challenges of Materials Management for CGTs
Part III: Biomanufacturer Use and Control of Polysorbates

Manufacturing, Impurities, and Characterization Methods Are Key Regulatory Focal Points for Peptides and OligonucleotidesAugust 9, 2021

Part I: Recent CMC/Regulatory Challenges of Oligonucleotide Drugs
Part II: Comparability Challenges in Crossing Over to Generics
Part III: Comparing Peptide and Oligonucleotide CMC Issues
Part IV: Starting Material Specifications for Oligonucleotides

Pandemic Intensifies USP’s Focus on Supply Chain Vulnerabilities and Vaccine Development — January 28, 2021 

Pandemic Spurs Deepening of Pharmacopoeia/Regulator/Industry Communication ChannelsDecember 23, 2020

Part I: EDQM Pandemic Actions Continue Apace in Fall 2020
Part II: Pharmacopeia, Regulator and Industry Expert Panel Explores Pandemic and Nitrosamine Communications
Part III: Second Panel Focuses on Pandemic Organizational Impacts and Key Learnings
Part IV: EDQM and Ph. Eur. Evolution Addressed by Leaders Keitel and Vielle

USP’s Global Efforts to Strengthen Standards and Accelerate Innovation for Biologics Include ICH EngagementNovember 9, 2020

Synthesis and Analysis Advancements Are Unleashing the Potential of Peptides and Oligos, Spurring CMC Regulatory DialogueJuly 23, 2020

USP Convention Meets Virtually in May 2020 to Review Upcoming Priorities, with Both 200-Year Legacy and Current Pandemic in FocusJuly 16, 2020

Attention Heightens on Creating an Independent Regulatory Pathway for Introducing Novel Excipients March 20, 2020

Part I: FDA’S Novel Excipient Program Proposal and Stakeholder Comments
Part II: IPEC/IQ Thought Leaders on the Novel Excipient Drivers
Part III: Subcutaneous Biotherapeutics, Pediatrics, and Delayed Release
Part IV: USP Initiatives Supporting Novel Excipient Development
Part V: Assessing and Managing Excipient Risks

The Processing and Formulation Complexities of Therapeutic Biologics Compel Heightened Focus on Excipient NeedsNovember 5, 2019

USP Views Early Broad Stakeholder Engagement as Essential in Developing Performance-Based Standards for BiologicsOctober 27, 2019

Cell and Gene Therapy Initiatives Prominent on Biomanufacturing Agenda of U.S. National Institute of Standards and TechnologyMarch 27, 2019

Pharmacopoeia/Industry/Agency Global Dialogue on Compendial Compliance and Harmonization Continues, with Medicine Availability at StakeFebruary 15, 2019

Technology Roadmapping Leads NIIMBL Project Expansion Across Biopharmaceutical Manufacturing/Analytics/Workforce LandscapeJanuary 11, 2019

FDA’s BLA Review Sheds Light on Evolution of Biotherapeutic Product Analytical Methods and Their RegulationNovember 12, 2018

NIST is at Intersection of Industry/Government/Academia Efforts to Support the “Ecosystem” Needed for Cell/Gene Therapy AdvancementJanuary 31, 2018


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